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Pursuing more efficient multifunctional treatment is the main challenge of preclinical nanoparticle-mediated theranostics research. Here, nanoscale magnetite vortex donut shape was synthesized as a platform, and then ultrasmall gold nanoparticles were successfully embedded into the nanoring surface, thereby obtaining gold-modified magnetic vortex donut (GMVD). GMVD has a high photothermal conversion efficiency (η = 42.2%), which makes it have excellent photothermal ablation effect on tumors both in vivo and in vitro. Simultaneously, GMVD forms reactive oxygen species (ROS) under the 808 nm laser triggering, inducing ferroptosis. The addition of gold element also makes GMVD have the effect of radiotherapy (RT) sensitization. In conclusion, the synergistic treatment of RT and PTT greatly enhanced tumor ablation, indicating that GMVD has good biocompatibility and antitumor efficacy. This work demonstrates that the proposed GMVD can be a high-performance tumor diagnosis and theranostic treatment agent and may have great potential for clinical application in the future.
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Using 7.33 fb^{-1} of e^{+}e^{-} collision data collected by the BESIII detector at center-of-mass energies in the range of sqrt[s]=4.128-4.226 GeV, we search for the rare decays D_{s}^{+}âh^{+}(h^{0})e^{+}e^{-}, where h represents a kaon or pion. By requiring the e^{+}e^{-} invariant mass to be consistent with a Ï(1020), 0.98
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The potent neurotoxic venom of the black widow spider contains a cocktail of seven phylum-specific latrotoxins (LTXs), but only one, α-LTX, targets vertebrates. This 130 kDa toxin binds to receptors at presynaptic nerve terminals and triggers a massive release of neurotransmitters. It is widely accepted that LTXs tetramerize and insert into the presynaptic membrane, thereby forming Ca2+-conductive pores, but the underlying mechanism remains poorly understood. LTXs are homologous and consist of an N-terminal region with three distinct domains, along with a C-terminal domain containing up to 22 consecutive ankyrin repeats. Here we report cryoEM structures of the vertebrate-specific α-LTX tetramer in its prepore and pore state. Our structures, in combination with AlphaFold2-based structural modeling and molecular dynamics simulations, reveal dramatic conformational changes in the N-terminal region of the complex. Four distinct helical bundles rearrange and together form a highly stable, 15 nm long, cation-impermeable coiled-coil stalk. This stalk, in turn, positions an N-terminal pair of helices within the membrane, thereby enabling the assembly of a cation-permeable channel. Taken together, these data give insight into a unique mechanism for membrane insertion and channel formation, characteristic of the LTX family, and provide the necessary framework for advancing novel therapeutics and biotechnological applications.
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Microscopia Crioeletrônica , Simulação de Dinâmica Molecular , Venenos de Aranha , Venenos de Aranha/química , Venenos de Aranha/metabolismo , Animais , Cátions/metabolismo , Cátions/química , Cálcio/metabolismo , Cálcio/química , Viúva Negra/química , Viúva Negra/metabolismo , Sequência de AminoácidosRESUMO
Objective: To investigate the clinicopathological features, molecular pathology characteristics, and prognosis of non-small cell lung carcinoma (NSCLC) exhibiting co-expression of p40 and thyroid transcription factor1 (TTF1). Methods: Clinical and pathological data of six NSCLC cases with co-expression of p40 and TTF1 diagnosed at the First People's Hospital of Xiaoshan District, Hangzhou, China from January 2016 to December 2023 were collected. Relevant literature was also reviewed. Results: NSCLC with co-expression of p40 and TTF1 commonly occurred in male smokers and had been in stage â ¢-â £ when diagnosis. Microscopic examination revealed that the tumor cells were arranged in solid nests and sheets with marked atypia and visible mitotic figures. There was no prominent evidence of keratinization or glandular formation. The tumor cells diffusely co-expressed p40 and TTF1, exhibiting a dual immunophenotype characteristic of both squamous cell carcinoma and adenocarcinoma. Molecular testing of four NSCLC co-expressing p40 and TTF1 revealed the presence of common EGFR mutations, as well as mutations of NRAS (mutation rate of 2.09%), EML4-ALK (mutation rate of 24.77%), and PIK3CA (exon 10 c.1658 G>C p.S553T, mutation rate of 4.32%). All six tumors were poorly differentiated, highly invasive, and associated with poor prognosis. Four of the six patients experienced widespread metastasis and died within 7 to 30 months after the diagnosis or initial treatment. Conclusions: NSCLC with co-expression of p40 and TTF1 exhibits distinct clinicopathological features, immunophenotypes, molecular alterations, and clinical outcomes, characterized by rapid progression and poor prognosis. Pathologists should be vigilant in recognizing this entity to avoid misdiagnosis and missed diagnosis.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fatores de Transcrição , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Masculino , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Receptores ErbB/metabolismo , Receptores ErbB/genética , Mutação , Prognóstico , Feminino , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Idoso , Fragmentos de Peptídeos , Epitopos ImunodominantesRESUMO
Rare yeast infections have been slowly increasing, given the increasing numbers of patients who are immunocompromised after hematopoietic stem cell transplantation. A considered approach to the complex, multidisciplinary management of infections that are caused by these pathogens is essential to optimize patient outcomes. We reported the management of two patients with combined rare yeast Trichosporon asahii infections, that suggested we should perform timely multivisceral screening for systemic dissemination of infection, and early treatment and combination of medications may improve prognosis.
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Aspergillus fumigatus , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Masculino , Aspergillus fumigatus/isolamento & purificação , Aspergilose/etiologia , Aspergilose/diagnóstico , Adulto , Feminino , Transplante Homólogo , Pessoa de Meia-Idade , Hospedeiro ImunocomprometidoRESUMO
Neurodegenerative diseases, originating from irreversible progressive loss of neuronal structure or function, are difficult to diagnose and treat. They vary widely in scope and have poor prevention and prognosis. Therefore, research on their early diagnosis is particularly important. Exosomes are small vesicles of cellular origin that contain various bioactive small molecules, such as proteins, RNAs, and DNAs, and play important roles in intercellular communication. Recent studies have shown that exosomes and their non-coding RNAs are key factors in the pathogenesis of various neurodegenerative diseases. Therefore, exosomes and their non-coding RNAs may provide a breakthrough for the early diagnosis of neurodegenerative diseases. This review summarizes the biology of exosomes and the current research progress of exosomes and their non-coding RNAs in diagnosing neurodegenerative diseases and further explores the challenges and prospects they face.
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Exossomos , Doenças Neurodegenerativas , RNA não Traduzido , Exossomos/metabolismo , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/diagnóstico , Humanos , RNA não Traduzido/genéticaRESUMO
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients'suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
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Controle de Qualidade , Transtornos da Articulação Temporomandibular , Transtornos da Articulação Temporomandibular/terapia , Transtornos da Articulação Temporomandibular/diagnóstico , Humanos , Estudos de Coortes , ConsensoRESUMO
OBJECTIVE: To explore the mechanism underlying the protective effect of Lonicerae japonicae flos (LJF) extract against doxorubicin (DOX) -induced liver injury in mice. METHODS: Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets, based on which the protein-protein interaction (PPI) network was constructed using STRING database for screening the core targets using Cytoscape software. DAVID database was used for bioinformatics analysis, and the core components and core targets were verified using molecular docking study. In a mouse model of DOX-induced liver injury, the effect of LJF extract on liver pathologies, serum levels of ALT and AST, and hepatic expressions of HYP, ROS, TNF-α, IL-6, COL-â £ and P53 proteins were evaluated using HE and Masson staining, ELISA, and Western blotting. RESULTS: We identified 12 core targets from 43 intersection genes involving cancer pathway, IL-17 signaling pathway, and TNF signaling pathways. Molecular docking study suggested that 10 core components of LJF could bind to different core targets. The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis, increased ROS content, and enhanced expressions of TNF-α, IL-6, HYP, COL-â £ and P53 proteins in the liver tissue. All these changes in the mouse models were significantly alleviated by treatment with LJF extract, suggesting obviously lowered levels of oxidative stress, inflammation and fibrosis in the liver tissues. CONCLUSION: LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53, TNF and IL-6 to reduce liver oxidative stress, inflammation and fibrosis.
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Doença Hepática Induzida por Substâncias e Drogas , Doxorrubicina , Interleucina-6 , Lonicera , Simulação de Acoplamento Molecular , Fator de Necrose Tumoral alfa , Animais , Doxorrubicina/efeitos adversos , Camundongos , Lonicera/química , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Extratos Vegetais/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Proteína Supressora de Tumor p53/metabolismo , Substâncias Protetoras/farmacologia , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacos , Farmacologia em RedeRESUMO
The J/ψ, ψ(3686)âΣ^{0}Σ[over ¯]^{0} processes and subsequent decays are studied using the world's largest J/ψ and ψ(3686) data samples collected with the BESIII detector. The parity-violating decay parameters of the decays Σ^{0}âΛγ and Σ[over ¯]^{0}âΛ[over ¯]γ, α_{Σ^{0}}=-0.0017±0.0021±0.0018 and α[over ¯]_{Σ^{0}}=0.0021±0.0020±0.0022, are measured for the first time. The strong CP symmetry is tested in the decays of the Σ^{0} hyperons for the first time by measuring the asymmetry A_{CP}^{Σ}=α_{Σ^{0}}+α[over ¯]_{Σ^{0}}=(0.4±2.9±1.3)×10^{-3}. The weak CP test is performed in the subsequent decays of their daughter particles Λ and Λ[over ¯]. Also for the first time, the transverse polarizations of the Σ^{0} hyperons in J/ψ and ψ(3686) decays are observed with opposite directions, and the ratios between the S-wave and D-wave contributions of the J/ψ, ψ(3686)âΣ^{0}Σ[over ¯]^{0} decays are obtained. These results are crucial to understand the decay dynamics of the charmonium states and the production mechanism of the Σ^{0}-Σ[over ¯]^{0} pairs.
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The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer (BTC), published in late 2022 were adapted in December 2023, according to established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with BTC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with BTC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Taiwan Oncology Society (TOS). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. Drug access and reimbursement in the different regions of Asia are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with BTC across the different countries and regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices and molecular profiling, as well as age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different countries.
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Neoplasias do Sistema Biliar , Humanos , Neoplasias do Sistema Biliar/terapia , Neoplasias do Sistema Biliar/diagnóstico , Neoplasias do Sistema Biliar/epidemiologia , Oncologia/normas , Ásia/epidemiologia , Guias de Prática Clínica como Assunto , Sociedades MédicasRESUMO
Using data samples collected with the BESIII detector at the BEPCII collider at center-of-mass energies ranging from 3.80 to 4.95 GeV, corresponding to an integrated luminosity of 20 fb^{-1}, a measurement of Born cross sections for the e^{+}e^{-}âD^{0}D[over ¯]^{0} and D^{+}D^{-} processes is presented with unprecedented precision. Many clear peaks in the line shape of e^{+}e^{-}âD^{0}D[over ¯]^{0} and D^{+}D^{-} around the mass range of G(3900), ψ(4040), ψ(4160), Y(4260), and ψ(4415), etc., are foreseen. These results offer crucial experimental insights into the nature of hadron production in the open-charm region.
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Objective: To investigate the effects of enriched environments on behavioral development at toddler period of preterm who had experienced early repeated operative pain. Methods: A cross-sectional study was conducted. A total of 80 high-risk preterm children of 2 years of age, who had experienced repeated pain stimuli in the neonatal intensive care unit (NICU), were enrolled as preterm group from the High-risk Children Clinic of Children's Hospital of Nanjing Medical University from October 2016 to March 2021. Furthermore, 39 full-term healthy children, aged 2 years, who were undergoing routine check-ups during the same period, were selected as the full-term group. The preterm group was further divided into preterm intervention group and preterm non-intervention group based on the implementation of enriched environment interventions. Data of neonatal characteristics from 3 groups were collected. Growth and development indicators at the age of 2 years were measured. Neuropsychological development evaluated by Gesell developmental scale. Behavioral development evaluated by child behavior check list. The salivary cortisol levels in response to novelty (baseline, task, end) were collected. The family environment, including maternal parenting pressure, were evaluated through a survey questionnaire. One-way ANOVA and least significant difference (LSD) tests were used to compare physical development, maternal parenting stress, Gesell neuropsychological development, and behavioral problems among the 3 groups. A repeated-ANOVA and LSD tests were employed to compare the patterns of salivary cortisol secretion. Pearson correlation analysis was used to explore the influencing factors related to neuropsychological and behavioral development and cortisol level. Results: There were 44 cases in the preterm intervention group (17 males, gestational age of (31.3±2.8) weeks), and 36 in the preterm non-intervention group (29 males, gestational age of (32.5±2.6) weeks). The full-term group consisted of 39 children (23 males, gestational age of (39.3±2.1) weeks). At 2 years of age, the height, weight, and head circumference of the preterm intervention group and non-intervention group were all lower than those of the full-term group (all P<0.05).The Gesell developmental schedule showed that the preterm non-intervention group scored all lower in gross motor, fine motor, adaptive, language and personal-social domains compared to the full-term group (91±7 vs. 97±6, 88±9 vs. 94±6, 89±8 vs. 99±8, 84±10 vs. 100±15, 89±7 vs. 95±6), with statistical significance (all P<0.01). The preterm intervention group scored all higher than the preterm non-intervention group in gross motor, fine motor, adaptive and language domains (all P<0.05), with no significant difference compared to the full-term group (all P>0.05). The number of needle painful procedures during hospitalization in NICU of the non-intervention group was negatively correlated to the adaptive development quotient (r=-0.48, P<0.05). Furthermore, the preterm non-intervention group exhibited higher scores in social withdrawal, depression, somatic complaints, aggression, and destructive behaviors compare to the full-term group and preterm intervention group (F=8.07, 5.67, 7.72, 7.90, 7.06; all P<0.05); while the preterm intervention group showed no significant difference compared to full-term group (all P>0.05). Behavioral problems (social withdrawal and depression) in the preterm non-intervention group were positively correlated with maternal parenting stress (r=0.66, 0.50; both P<0.05). In response to novel visual stimuli and cognitive challenges, the preterm non-intervention group had significantly higher salivary cortisol levels compared to the full-term group (P=0.006), which were negatively correlated with the frequency of early painful procedures (r=-0.83, -0.80; both P<0.01). There was no significant difference in cortisol secretion pattern between the intervention group and the full-term group (P=0.772). Conclusion: Enriched environmental interventions can improve neuropsychological development, decrease behavioral problems, and down-regulate consistent high cortisol response to task in preterm infants who have experienced repeated procedural pain in the NICU by the age of 2 years.
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Desenvolvimento Infantil , Recém-Nascido Prematuro , Dor Processual , Humanos , Estudos Transversais , Pré-Escolar , Recém-Nascido , Feminino , Masculino , Dor Processual/etiologia , Unidades de Terapia Intensiva Neonatal , Lactente , Comportamento Infantil , Hidrocortisona/análise , Hidrocortisona/metabolismo , Saliva/metabolismo , Meio Ambiente , Mães/psicologiaRESUMO
Objective: To evaluate the clinical effect of bispherical augment in acetabular defects reconstruction in hip revision. Methods: This is a retrospective case series study. A retrospective analysis of 119 patients (124 hips) patients who underwent hip revision surgery and reconstructed with bispherical augment for acetabular bone defects from January 2019 to December 2023 was performed. There were 57 males (58 hips) and 62 females (66 hips), aged (65.0±11.8) years (range:40 to 102 years). The body mass index was (23.9±3.5) kg/m2 (range:16.1 to 32.2 kg/m2). Acetabular bone defects were typed as follows: 2 hips in Paprosky type â ¡A, 29 hips in type â ¡B, 34 hips in type â ¡C, 31 hips in type â ¢A, and 28 hips in type â ¢B, of which 9 patients (9 hips) were combined with pelvic discontinuity. Differences in Harris hip score (HHS) and lower limb discrepancy (LLD) were compared between preoperatively and final follow-up. The height of the hip center of rotation and the horizontal distance from the center of rotation to the teardrop were measured by radiographs before and after surgery, and prothesis stability and the occurrence of postoperative complications were evaluated. Data were compared using the paired sample t test. Results: All patients successfully completed the operation. The operation time was (167.0±53.4) minutes (range:90 to 380 minutes) and the intraoperative bleeding was (345.3±124.2) ml (range:100 to 1 200 ml). The height of the hip center of rotation decreased from (39.7±13.0) mm preoperatively to (21.8±7.1) mm postoperatively and the horizontal distance from the center of rotation to the teardrop increased from (34.0±10.1) mm preoperatively to (38.5±5.9) mm postoperatively, and the differences were statistically significant (t=15.859, P<0.01; t=5.266,P<0.01). All the patients were followed up for (26.1±15.4) months (range:6 to 60 months). At the last follow-up, HHS improved from (35.2±10.0) points preoperatively to (85.5±9.5) points, and the difference was statistically significant (t=50.723,P<0.01). LLD decreased from (2.1±1.1) cm preoperatively to (0.5±0.5) cm, and the difference was statistically significant (t=13.767, P<0.01). All acetabular components were stable and free of displacement on imaging during follow-up. Three patients suffered dislocation and received closed reduction, all prosthesis were in good position during follow-up. No dislocation, loosening, fracture, recurrence of infection and vascular nerve injury occurred in other patients. Conclusion: Bispherical augment can effectively reconstruct acetabular bone defects, restore the hip center of rotation, and improve hip joint function scores at short and mid-term follow-up.
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Acetábulo , Procedimentos de Cirurgia Plástica , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Acetábulo/cirurgia , Idoso , Adulto , Procedimentos de Cirurgia Plástica/métodos , Idoso de 80 Anos ou mais , Resultado do TratamentoRESUMO
On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E_{QG,1}>10 times the Planck energy E_{Pl} for the linear LIV effect, and E_{QG,2}>6×10^{-8}E_{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.
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Objective: To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts. Methods: C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry. Results: On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant (Pï¼0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant (Pï¼0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all Pï¼0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8+ T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, Pï¼0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, Pï¼0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, Pï¼0.05]. The proportion, of CD4+ T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, Pï¼0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, Pï¼0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all Pï¼0.05). Conclusion: High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.
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Carcinoma Pulmonar de Lewis , Dieta com Restrição de Carboidratos , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Microambiente Tumoral , Animais , Carcinoma Pulmonar de Lewis/radioterapia , Carcinoma Pulmonar de Lewis/metabolismo , Camundongos , Dieta Hiperlipídica/efeitos adversos , Dieta com Restrição de Carboidratos/métodos , Carga Tumoral , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologiaRESUMO
Objective: This investigation sought to delineate the associations among colorectal adenomatous polyps, diabetes, and biomolecules involved in glucose metabolism. Method: Data were collected from 40 patients who underwent endoscopic polypectomy at the Endoscopy Department of Shandong Cancer Hospital between June 2019 and September 2021. This cohort included 27 patients with inflammatory polyps and 13 with adenomatous polyps. We assessed fasting insulin (Fins), fasting blood glucose (FBG), and the mRNA expressions of fibroblast growth factor 19 (FGF-19) and insulin-like growth factor 1 (IGF-1) in the polyp tissues. Both univariate and multivariate logistic regression analyses were employed to ascertain the determinants influencing the emergence of adenomatous polyps. From these analyses, a predictive nomogram was constructed to forecast the occurrence of adenomatous polyps, and evaluations on the discriminative capacity, calibration, and clinical utility of the model were conducted. Results: The adenomatous polyp group exhibited markedly elevated levels of glucose, insulin, FGF-19, and IGF-1, with respective concentrations of (8.67±2.70) mmol/L, (12.72±7.69) µU/L, 2.20±1.88, and 1.36±0.69. These figures were significantly higher compared to the inflammatory polyp group, which showed levels of (5.51±0.72) mmol/L, (5.49±2.68) µU/L, 0.53±0.97, and 0.41±0.46, respectively, P=0.001. Multivariate logistic regression revealed that the relative expression of IGF-1 served as an independent risk factor for the development of colorectal adenomatous polyps (OR=5.622, 95% CI:1.085-29.126). The nomogram displayed a C-index of 0.849, indicating substantial discriminative capability. The calibration curve affirmed the model's accuracy in aligning predicted probabilities with actual outcomes, and the clinical decision curve demonstrated thepractical clinical applicability of the model. Conclusions: There was a significant correlation between the occurrence of colorectal adenomatous polyps and glucose metabolic pathways. Individuals with diabetes showed a higher propensity to develop such polyps.
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Pólipos Adenomatosos , Glicemia , Neoplasias Colorretais , Fatores de Crescimento de Fibroblastos , Fator de Crescimento Insulin-Like I , Insulina , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Neoplasias Colorretais/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Glicemia/metabolismo , Insulina/metabolismo , Pólipos Adenomatosos/metabolismo , Pólipos do Colo/metabolismo , Masculino , Feminino , Adenoma/metabolismo , Pessoa de Meia-Idade , Modelos Logísticos , Nomogramas , Peptídeos Semelhantes à InsulinaRESUMO
Objective: To compare the clinical effect of modified anterolateral and traditional acromioplasty in arthroscopic rotator cuff repair. Methods: The clinical data of 92 patients with total rotator cuff tears admitted to the Department of Joint Surgery of Jinhua Central Hospital from January 2016 to December 2019 were retrospectively analyzed. Of the patients, 42 were male, 50 were female, with a mean age of (57.1±13.2) years. Among them, 42 patients underwent traditional acromioplasty during arthroscopic rotator cuff repair (traditional group), and 50 underwent modified anterolateral acromioplasty (modified group). The preoperative and postoperative shoulder function of the patients in the two groups were evaluated and compared by using the University of California Los Angeles (UCLA), the rating scale of the American Shoulder and Elbow Surgeons (ASES), and the constant Murley shoulder score scale. And the preoperative and postoperative pain of patients was evaluated with visual analog scale (VAS). The incidence of rotator cuff retears 12 months after operation was counted. Results: There was no statistically significant differences in general information such as gender, age, affected side and course of disease between the two groups before the surgery (all P<0.05). All patients were followed up for (12.9±1.1) months. There was no significant differences in the UCLA score (31.4±3.0 vs 32.0±2.5), ASES score (13.1±0.7 vs 13.3±0.6), Constant Murley shoulder score (92.1±6.6 vs 94.3±4.6) and VAS score (1.5±0.8 vs 1.2±1.1) between the traditional group and the modified group 12 months after the operation (all P>0.05). The preoperative CSA (36.0°±1.7°) in the traditional group did not differ significantly from that at 12 months postoperatively (35.5°±1.2°) (P=0.270); the postoperative CSA at 12 months (30.8°±2.5°) in the modified group was significantly smaller than that before the operation (36.5°±1.9°), and also was smaller than that in the traditional group 12 months after the operation (35.5°±1.2°) (both P<0.05). At 12 months after operation, the rate of rotator cuff tears in the traditional group and modified group was 16.7% (7/42) and 4.0% (2/50), respectively (P=0.045). Conclusions: Traditional and modified anterolateral acromioplasty in treating total rotator cuff tears using arthroscopic rotator cuff repair can significantly improve shoulder joint function. However, modified anterolateral acromioplasty significantly reduces the CSA value and decreases the incidence of rotator cuff re-tears.
Assuntos
Artroscopia , Lesões do Manguito Rotador , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Lesões do Manguito Rotador/cirurgia , Artroscopia/métodos , Acrômio/cirurgia , Resultado do Tratamento , Manguito Rotador/cirurgia , Articulação do Ombro/cirurgia , Artroscópios , IdosoRESUMO
In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.
RESUMO
OBJECTIVE: Observational studies have suggested an association between chronic periodontitis (CP) and chronic obstructive pulmonary disease (COPD). This study aimed to determine whether there is a causal relationship between CP and COPD incidence. DESIGN: Twosample Mendelian Randomization (MR) analysis using summary statistics from two genomewide association studies (GWASs) of European ancestry. Single nucleotide polymorphisms (SNPs) associated with COPD were obtained from the FinnGen database, which included 16,380,382 SNPs. The diagnosis of COPD was based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2023). We also obtained SNPs associated with CP from the FinnGen database, which included 16,380,378 SNPs. RESULTS: Sixteen eligible SNPs were extracted to analyze the causal effect of CP on COPD incidence. There was no causal correlation between CP and COPD using the inverse variance-weighted method (IVW) (OR=0.97, 95%CI= 0.91-1.05; p=0.482). Seven eligible SNPs were extracted to analyze the causal effect of COPD on CP incidence. Again, there was also no causal correlation between using IVW (OR=1.09, 95%CI=0.93-1.28; p=0.279). CONCLUSION: We did not demonstrate a causal relationship between genetically predicted CP and COPD, or between genetically predicted COPD and CP.